Patients with peripheral arterial disease (PAD) experience significant functional limitations due to ischemic symptoms (claudication) and are at high risk for CVD morbidity and mortality resulting from untreated cardiovascular disease (CVD) risk factors and aggressive atherosclerosis. The overall Goal of this randomized controlled clinical trial is to examine the synergistic effect of a multifactor risk reduction program based on components of a chronic care delivery system (i.e. clinical decision support, planned and structured visits, follow-up, application of behavioral change theories, use of a multidisciplinary team approach and self-management) on improving clinical and biological outcomes in 300 patients with PAD. Specifically, we will compare the effects of 24 months of a novel, yet well-tested multiple risk factor reduction program, the Health Education and Risk Reduction Training (HEAR2T) Program for PAD versus enhanced standard care on: 1) symptom limited walking distance as assessed by treadmill exercise testing and walking impairment questionnaire; 2) endothelial function as measured by flow mediated vasodilation (FMVD) via brachial artery ultrasound. We will also explore the association between FMVD and decreased oxidative stress (as measured by oxygen radical absorbance capacity and urinary isoprostanes) and reduced degradation of nitric oxide (NO) and/or increased NO biosynthesis (as measured by urine nitrogen oxide, plasma nitrogen oxide, plasma asymmetric dimethylarginine, plasma, urine and platelet cyclic GMP). Secondary hypotheses examine the association between reducing CVD risk factors, improved endothelial function, increased walking distance, improved quality of life and number of metabolic syndrome abnormalities in PAD patients. This study will contribute to the overall mission of NINR and to nursing science by providing the necessary evidence for the efficacy of a commonly utilized nursing intervention, multiple risk factor reduction, on improving physical function and quality of life in the understudied, elderly PAD patient. This application will also provide preliminary evidence for the biological basis for the efficacy of multifactor risk reduction in restoring vascular homeostasis, critical because of its role in antiatherogenesis and maintaining vasoreactivity, both necessary for slowing the progression of atherosclerosis. The relevance of this study to public health. People with PAD are at increased risk for death and disability because of severe atherosclerosis resulting from untreated CVD risk factors. This maybe due to health care systems that are not equipped to handle the problem. This study will examine the effect of a system that assists providers to reduce a patient's CVD risk factors and explores the biological reasons that this system may be effective in improving health. [unreadable] [unreadable] [unreadable]